It has been known for some time that molecules of various molecular weights can be separated across a semi-permeable membrane. The membrane by virtue of its composition, and consequently its porosity, allows molecules equal to or less than a particular molecular weight to pass through the membrane. Larger molecules are unable to pass through. This has led to four common applications of dialysis membranes: 1) exchanging one sample buffer for another buffer, 2) sample desalting, 3) molecular separations, and 4) sample concentration. These applications are most often utilized in the area of laboratory research and the dialysis of patient bodily fluids such as blood.
Various methods have been developed so that a dialysis membrane is the sole pathway of molecular exchange between a sample and dialysate. The most widely used method in the research laboratory is taking the dialysis membrane which is molded in the shape of a tube and tying, or clamping, one end of the tube to form a sack. The sample solution is added to the interior of the dialysis membrane sack which is then tied or clamped at the other end which had remained open. The sack, now a closed vessel, is submerged into the dialysate.
The method described above has significant drawbacks. The tying or clamping of the ends of the dialysis membrane tubing requires skill. If the end of the tubing is not carefully tied, the sack will leak and the sample can be lost. Also, it is difficult to load and unload the sample from the sack because the membrane is flaccid; samples are often spilled during these steps. Touching the dialysis tubing membrane with fingers can also affect the sample dialysis. Therefore it requires skill to touch as little of the membrane as possible when tying or clamping it. An alternative is to wear gloves; however, it also requires skill to tie the tubing while wearing gloves. Since the sample chamber of the dialysis tubing membrane is open during the loading and unloading of sample, the sample can be contaminated with any substance in the environmental air. It would be desirable to have a sample chamber which is hermetically sealed and to add the sample with a device such as a syringed needle. Also, wetted dialysis membrane tubing can not be labeled so labeling must be written on a small clamp or on an object which is inconveniently attached to the tubing with material such as string.
In order to address some of the problems with loading sample into and unloading sample from dialysis tubing as described above, one company has offered commercially preformed dialysis sacks. These sacks are dialysis tubing which has already been clamped at one end and at the open end a funnel has been attached. After the sample is loaded through the funnel, the tubing is clamped below the funnel and dialysis proceeds. Although the loading and unloading of sample are somewhat simplified, the product still suffers the other problems as described above for dialysis tubing.
Another commercially available product has taken another approach to addressing some of the inconvenience of the dialysis tubing and the pre-formed dialysis tubing sack. Two concentric rings, one larger than the other, trap a sheet of membrane between the rings when the outer ring is tightened upon the inner ring. A vessel is formed such that the rings form the walls of the vessel and the floor is the dialysis membrane. The vessel then is floated on top of the dialysate and sample is added to the interior of the floating vessel. Although this solution offers advantages, it introduces new problems. First, the sample may be open to the environmental air which would allow it to be easily contaminated. Secondly, because the vessel is open, it is easy for the sample to spill into the dialysate as it floats. Loading and unloading are greatly simplified, but assembly of the device requires some skill by the user.
Of the devices described above, none permit the convenient loading and unloading of small, fixed-volume samples to be dialyzed in the research laboratory. Also, none protect the sample from contamination during loading and unloading. To address these disadvantages, U.S. Pat. No. 5,503,741 owned by Pierce Biotechnology Incorporated discloses a dialysis device having a hermetically sealed vacant chamber. The chamber is formed by a gasket with dialysis membranes affixed to each side in facing relationship. The gasket is impermeable to the sample being dialyzed, but is penetrable and reusable such that a sample introduction mechanism can be inserted through the gasket into the chamber and then withdrawn without the sample being permitted to leak. In this fashion, convenient loading and unloading of small, fixed-volume samples into the chamber is accomplished while avoiding contamination. This application provides further enhancements to the dialysis device having a hermetically sealed chamber.